Online - 2455-3891 Print - 0974-2441 Vol 9, Suppl. 3, 2016 DOCKING STUDIES ON ANTIDIABETIC MOLECULAR TARGETS OF PHYTOCHEMICAL COMPOUNDS OF SYZYGIUM CUMINI (L.) SKEELS SMRUTHI G, MAHADEVAN V, VADIVEL V*, BRINDHA P Centre for Advanced Research in Indian System of Medicine, School of Chemical and Biotechnology, SASTRA University, Thanjavur, Tamil Nadu, India. Email: vadivel@carism.sastra.edu Received: 27 August 2016, Revised and Accepted: 14 September 2016 ABSTRACT Objectives: Different parts of jamun tree (Syzygium cumini L. skeels) which belongs to the family - Myrtaceae are well-known for their antidiabetic activity. Traditional practitioners in India are using the leaf, bark, and fruits of this medicinal plant over many centuries to manage the diabetic patients. Although several research works have been conducted to prove the efficacy of this plant extracts and also to explore the active principles of this plant drug, there is no information regarding the interaction of phytoconstituents of jamun tree with diabetic targets at the molecular level. Hence, this study focused to apply a computational approach to reveal the interaction of molecules of jamun tree with antidiabetic targets. Methods: Lamarckian genetic algorithm methodology was used for docking of 22 phytoconstituents with α-amylase, a key enzyme that involved in carbohydrate metabolism using Autodock software. Results: Analysis of binding energy of ligands with target receptors was remarkably lower especially for friedelin (−9.54 kcal/mol), epifriedelanol (−8.98 kcal/mol), betulinic acid (−8.60 kcal/mol), beta-sitosterol (−8.56 kcal/mol), petunidin-3-gentiobioside (−7.52 kcal/mol), kaempferol (−7.08 kcal/mol), petunidin (−6.21 kcal/mol), quercetin (−6.03 kcal/mol), myricetin (−5.80 kcal/mol), and bergenin (−5.27 kcal/mol) when compared to the synthetic drug acarbose (−2.43 kcal/mol). Conclusion: Potential molecules identified from this study could be considered as a lead to design/synthesize anti-diabetic drug molecules in pharmaceutical industry. Keywords: Jamun tree, Syzygium cumini, Phytochemicals, Diabetes, α-amylase, Molecular docking. INTRODUCTION Pancreatic α-amylase (E.C. 3.2.1.1) is a key enzyme in the digestive system and catalyses the initial step in hydrolysis of starch to maltose and finally to glucose. Degradation of this dietary starch proceeds rapidly and leads to elevated post-prandial hyperglycemia. Human pancreatic α-amylase in the small intestine correlates to an increase in post-prandial glucose levels, the control of which is therefore an important aspect in the treatment of diabetes [1]. Hence, retardation of starch digestion by inhibition of enzymes such as α-amylase would play a key role in the control of diabetes. However, the discovery of specific high-affinity inhibitors of pancreatic α-amylase for the development of therapeutics has remained elusive. Inhibitors currently in clinical use (e.g., acarbose, miglitol, and voglibose) are known to inhibit a wide range of glucosidases such as α-glucosidase and α-amylase. Because of their non-specificity in targeting different glucosidases, these hypoglycemic agents have their limitations and are known to produce serious side effects. Therefore, the search for safer, specific, and effective hypoglycemic agents has continued to be an important area of investigation with natural extracts from readily available traditional plant medicines offering great potential for discovery of new anti- diabetic drugs [2]. While plant derivatives with purported hypoglycemic properties have been used in folk medicine and traditional healing systems, very few of these traditional anti-diabetic plants have received proper scientific scrutiny despite recommendations by the World Health Organization. Ayurveda and other Indian traditional approaches have described more than 800 plants in the Indian subcontinent, known to possess anti- diabetic potential. In fact, only a few of them have been characterized for their mechanistic actions [3,4]. Syzygium cumini (L.) Skeels. (Syn: Eugenia jambolana Lam., Family: Myrtaceae) is one of the widely used plants for the treatment of diabetes by traditional practitioners over many centuries. It is commonly known as jambolan, black plum, java plum, Indian blackberry, Portuguese plum, Malabar plum, purple plum, Jamaica, and damson plum. It is a large evergreen and densely foliaceous tree with greyish-brown thick bark, exfoliating in woody scales. The wood is white; leaves are leathery, oblong-ovate to elliptic or obovate-elliptic with 6-12 cm long, the tip being broad and less acuminate. Flowers are scented, greenish-white, found in clusters and are round or oblong shaped in dichotomous paniculate cymes. The fruits are berries and are often obviously oblong, 1.5-3.5 cm long, dark- purple or nearly black, luscious, fleshy and edible, which contains a single large seed (Fig. 1). Sagrawat et al. [5] reviewed the pharmacological actions and phytochemical constituents of jambolan. Various extracts of jambolan possess a range of pharmacological actions, viz., antibacterial, antifungal, antiviral, antigenotoxic, anti-inflammatory, antiulcerogenic, cardioprotective, antiallergic, anticancer, chemopreventive, radioprotective, free radical scavenging, antioxidant, hepatoprotective, antidiarrheal, hypoglycemic and antidiabetic effects [6]. Clinical and experimental studies of jambolan revealed that different parts of the plant especially fruits, seeds and stem bark possess promising antidiabetic activity. In the early 1960-1970s, some preliminary reports on the antidiabetic activity of different parts of jambolan in experimental animals have been reported [7-9]. Seeds were considered as more effective in experimental diabetes as they quickly reduced the sugar level in urine [10]. Administration of seed extracts caused hypoglycemia in mild and severe diabetic rabbits [11]. Seed methanolic extract showed inhibition in murine liver glucosidases activity [12]. Oral administration of seed extract to rats for 15 days lowered the blood glucose [13]. The ethanolic extract of seeds decreased blood sugar levels in alloxan induced diabetic rats [14]. Research Article © 2016 The Authors. Published by Innovare Academic Sciences Pvt Ltd. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4. 0/) DOI: http://dx.doi.org/10.22159/ajpcr.2016.v9s3.14920